Correspondence

Guidelines for pregnant Pregnant individual with suspected monkeypox exposure

• Travelled to an affected country within the previous 21 days
individuals with • Close contact with a confirmed case of monkeypox (ie, living together, sexual contact, or contact with
body fluids and contaminated linen)
Published Online
monkeypox virus • Exposure to unusual or exotic pets
June 21, 2022
https://doi.org/10.1016/
exposure Clinical examination (including skin, vagina, and oral mucosa)
S0140-6736(22)01063-7
Airborne and contact PPE during patient evaluation
On May 21, 2022, WHO reported
an emerging global outbreak of For more on the 2022
monkeypox virus infection, with monkeypox outbreak see
Asymptomatic Symptomatic https://www.who.int/
documented community transmission • Skin rash*, genital lesions emergencies/disease-outbreak-
among people in contact with • Fever >38°C, headache, lymphadenopathy news/item/2022-DON385
• Sore throat, mouth or throat lesions
symptomatic cases in non-endemic
countries.
The likelihood of infection in Monkeypox real-time PCR Monkeypox real-time PCR
Oropharyngeal swab (blood, vaginal fluid, or urine Swabs of any suspicious skin or mucosal lesion
pregnant women is high because of can be considered) (surface or exudate)
post-COVID-19 border reopening
and travel among countries presently
experiencing an outbreak. Monkeypox negative Monkeypox positive Monkeypox negative Monkeypox positive
Human infections with monkeypox
and smallpox (a closely related
Isolation at home for 21 days Isolation at home for 21 days
orthopoxvirus) can carry a high • No visitors • No visitors
risk of severe congenital infection, • Clinical self-monitoring (temperature • Clinical self-monitoring
and rash) • Rule out other potential causes†
pregnancy loss, and maternal • Discuss orthopox vaccine (best within • If symptoms persist: retest
morbid­ i ty and mortality. 1 Of 4 days of exposure but can be up to
14 days in the absence of symptoms)
four pregnant women from the
Democratic Repub­lic of the Congo
infected with monkey­ p ox virus Ultrasound fetal surveillance Hospitalisation in a tertiary or designated
centre (if clinically indicated)
(probably with the central African • Growth and umbilical artery Doppler
scans monthly WHO clinical severity score
clade of the virus) between 2007 and • Discuss amniocentesis if signs of • Mild (<25 skin lesions)
2011, two had spontaneous early hydrops or hepatomegaly • Moderate (25–99 skin lesions)
• Severe (100–250 skin lesions)
miscarriages, and one had a second- • Grave (>250 skin lesions)
trimester loss at 18 weeks’ gestation.2 Maternal surveillance
The stillborn fetus had a generalised Stop monitoring Recovery
• Temperature, heart rate, blood pressure
(3–4 times per day), plus supportive care and
skin rash, and monkeypox virus DNA pain management
detected in fetal tissue, umbilical • Antibiotics (systemic amoxicillin,
chloramphenicol via eye drops) to prevent
cord, and placenta, confirming bacterial superinfection
vertical transmission of monkeypox • Tecovirimat, vaccinia immune globulin, and
orthopox vaccine
virus. Genomic sequencing data • Cidofovir considered only in critically ill pregnant
suggest the west African clade of women (teratogen)
Fetal
monkeypox virus is responsible for • Fetal assessment (FHR) and corticosteroid use
the current outbreak; although it for fetal lung maturation depending on
gestational age
is associated with milder disease
and a lower case fatality rate in
Delivery (high risk of preterm birth)
• On site or IRNP
• Caesarean section probably not superior to
vaginal delivery, except if genital lesions present
Figure: Clinical management algorithm for • Consider monkeypox viral load assessment from
suspected monkeypox virus exposure during umbilical cord blood and placenta
pregnancy Newborn
FHR=fetal heart rate. IRNP=isolation room with • Early cleaning of the newborn
negative pressure. PPE=personal protective • Newborn monitoring in IRNP
equipment. *Higher suspicion if skin rash is • Monkeypox real-time PCR of the newborn (any
suspicious mucocutaneous lesions, or: eye,
concentrated over the genitals, face, and extremities. Submissions should be
nasopharynx, mouth, rectum, perineal area,
†PCR should be done from a vesicle or genital lesion. made via our electronic
and infant/umbilical cord blood)
We also suggest PCR for herpes simplex virus, • Depending on local policy, infant separation submission system at
varicella zoster virus, and syphilis to rule out other should be discouraged where possible http://ees.elsevier.com/
causes of vesiculopustular rash in pregnancy. thelancet/

www.thelancet.com Vol 400 July 2, 2022 21

 Correspondence
non-pregnant people, the effects of
this clade in pregnancy are unknown.
Here, we propose a clinical
management algorithm for pregnant
women with suspected monkeypox
virus exposure (figure). Clinicians
must maintain a high index of
suspicion for monkeypox virus in any
pregnant woman presenting with
lymphadenopathy and vesiculo­pustular
rash—including rash localised to the
genital or perianal region—even if
there are no apparent epidemiological
links. Diagnosis is confirmed by
nucleic acid amplification testing
with real-time or conventional PCR
for monkeypox virus from vesicles or
genital lesions; additionally, we advise
ruling out varicella, herpes simplex,
and syphilis, as these might resemble
monkeypox in pregnancy. Fetal
ultrasound monitoring is required
in cases of maternal monkeypox
virus infection, and subsequent
management should be based on the
presence of ultrasound anomalies such
as fetal hepatomegaly or hydrops.
Monkeypox can have considerable
risks to the fetus, so we also suggest
testing asymptomatic pregnant
women with significant monkeypox
virus exposure to identify those who
require fetal ultrasound follow-up.
The sensitivity of molecular detection
of monkeypox virus in the amniotic
fluid is unknown. By analogy with
For WHO’s monkeypox cytomegalovirus, toxoplasmosis,
outbreak situation update see and Zika virus infections, it is likely
https://www.who.int/
emergencies/disease-outbreak-
that monkeypox virus is shed in the
news/item/2022-DON393 amniotic fluid only once the fetal
kidneys produce sufficient urine (ie,
after 18–21 weeks’ gestation).3 At
delivery, we recommend assessing
viral load in umbilical cord blood and
placenta and real-time PCR analysis of
specimens obtained from the neonate.
For treatment, tecovirimat and
vaccinia immune globulin can be
considered for pregnant women
who are severely ill. Tecovirimat is
an inhibitor of the orthopoxvirus
VP37 envelope wrapping protein.
The European Medicines Agency has
approved tecovirimat for monkeypox,
22 www.thelancet.com Vol 400 July 2, 2022
and tecovirimat can be used in the
USA under an expanded access
Investigational New Drug protocol for
the empirical treatment of non-variola
orthopoxvirus infections, including
monkeypox. The US Food and Drug
Administration (FDA) prescribing
information for tecovirimat confirms
that no embryotoxic and teratogenic
effects have been detected in animal
studies. Furthermore, the US Centers
for Disease Control and Prevention4
permits the emergency use of the
live smallpox vaccine ACAM2000,
which confers 85% cross-protective
immunity against monkeypox, if high-
risk exposure to monkeypox virus
occurs in pregnancy. Patients must,
however, be counselled on the rare
risk of fetal vaccinia from ACAM2000,
which can result in preterm delivery,
stillbirth, neonatal death, and potential
adverse maternal reactions. MVA-BN,
a third-generation smallpox vaccine
recently approved in the USA, Canada,
and the EU, is possibly safer because it
contains non-replicating virus and has
not demonstrated adverse pregnancy
outcomes.5 Finally, we encourage the
reporting of all cases of monkeypox
virus in pregnancy to WHO and an
international registry for emerging
pathogens.6
These recommendations should
be adapted to local guidelines and
updated as more information arises.
We declare no competing interests.
Pradip Dashraath,
Karin Nielsen-Saines, Citra Mattar,
Didier Musso, Paul Tambyah,
*David Baud
david.baud@chuv.ch
Division of Maternal-Fetal Medicine, Department of
Obstetrics and Gynecology, National University
Hospital, Singapore (PD, CM); Yong Loo Lin School of
Medicine, National University of Singapore,
Singapore (PD, CM, PT); Division of Infectious
Diseases, Department of Medicine, National
University Hospital, Singapore (PT); Division of
Pediatric Infectious Diseases, Department of
Pediatrics, David Geffen School of Medicine, UCLA,
Los Angeles, CA, USA (KN-S); Aix Marseille Université,
IRD, AP-HM, SSA, VITROME, IHU – Méditerranée
infection, Marseille, France (DM); Laboratoire
Eurofins Labazur Guyane, French Guiana (DM);
Materno-fetal and Obstetrics Research Unit,
Department Woman-Mother-Child, Lausanne
University Hospital (CHUV), 1011 Lausanne,
Switzerland (DB)
1 Nishiura H. Smallpox during pregnancy and
maternal outcomes. Emerg Infect Dis 2006;
12: 1119–21.
2 Mbala PK, Huggins JW, Riu-Rovira T, et al.
Maternal and fetal outcomes among pregnant
women with human monkeypox infection in
the Democratic Republic of Congo. J Infect Dis
2017; 216: 824–28.
3 Vouga M, Musso D, Mieghem TV, Baud D. CDC
guidelines for pregnant women during the
Zika virus outbreak. Lancet 2016; 387: 843–44.
4 US Centers for Disease Control and Prevention.
Vaccinia (smallpox) vaccine: recommendations
of the Advisory Committee on Immunization
Practices (ACIP), 2001. MMWR Recomm Rep
2001; 50: 1–26.
5 UK Health Security Agency. Recommendations
for the use of pre and post exposure
vaccination during a monkeypox incident.
June 6 2022. https://www.gov.uk/
government/publications/monkeypox-
vaccination (accessed June 15, 2022).
6 Panchaud A, Favre G, Pomar L, et al.
An international registry for emergent
pathogens and pregnancy. Lancet 2020; 395:
1483–84.
Monkeypox genomic
surveillance will
challenge lessons learned
from SARS-CoV-2
The emergence of a series of
epidemiologically connected monkey­
pox virus infections around the world,
with ongoing human-to-human
transmission (as of June 15, 2022,
2103 confirmed cases, one probable
case, and one death have been
reported to WHO from 42 countries),
raises concerns of a long-apprehended
comeback of a human-adapted
orthopoxvirus related to variola virus,
the aetiological agent of smallpox.
Since variola virus had no natural
reservoir other than humans, the
eradication of the virus by use of
highly effective vaccines against
orthopoxviruses was irreversible. 1
However, other orthopoxviruses have
reservoirs in wildlife, such as cowpox
virus (in voles), taterapox virus (in
African gerbils), and monkeypox
virus (in small mammals), do have
the potential to spill into the human
population and facilitate a restart of
the genetic adaptation of the virus to